The present invention relates to a reactor equipped with a cover that is generally used for a chemical reaction container, or preferably for a reaction container utilized with an apparatus in which contamination of specimen must be avoided.
Of late, a diagnosis of infectious disease, hereditary disease or cancer has become possible through gene analysis. In a gene analysis, where genes are extracted from a blood, sputum or tissue sample of a patient and a specific formation of the gene is detected, diagnosis is made in a relatively short time. The analysis requires a certain quantity of genes and, if few are available for the analysis, genes are reproduced in a large quantity so that the detection can be done.
Polymerase chain reaction (PCR) is the most popular method for reproduction of genes in a large quantity. An automated heat cycler designed for simultaneous PCR of a number of specimens is described in the U.S. Pat. No. 5,038,852. According to the patent, reaction containers are arranged typically 6 by 8 or 8 by 12.
These reaction containers are inserted into a metal block so that the bottom of each container thermally contacts the block evenly. Then, the temperature of the metal block is varied according to the specified temperature and duration of the PCR protocol.
In the first stage of the PCR, reaction solution is heated and maintained at about 95xc2x0 C. In this process, the reaction container is covered with a cap to prevent evaporation of the reaction solution and then heated over the cap. The cap can be a separate individual cap or may be connected as a part to the reaction container.
The cap, which is, for example, of a dome shape on the top and a pipe shape on the bottom, is inserted into the reaction container so as to contact the inside closely to seal the container. The cap can be removed by pulling up one end of each cap strip.
Capping and uncapping are troublesome and time-taking task because they must be done very carefully so as to prevent contamination inside the reaction container or from a reaction container to another.
In conducting the PCR, capped reaction containers are inserted into the metal block and the heating plate is lowered onto the block. In this process, the heating plate pushes down the dome-shaped caps to let the caps be seated evenly onto all reaction containers and each reaction container thermally contact the metal block favorably. Then, in order to prevent condensation of the vapor inside reaction container or the caps, the heating plate is maintained at higher temperature than any other in the PCR protocol.
When the reaction solution is cooled down sufficiently after the PCR is complete, the capped reaction containers are taken out of the heat cycler. Then, the reaction containers are uncapped by pulling up each cap strip. The obtained PCR product, for example, in case of a gene analysis, is then handed over to the next process for detection.
Another example of a reaction container is described in the Japanese Patent Application Laid-Open No. 7-5180 (1995). A plane array of a reaction container cover is described in the Publication. According to the description, the cover is a flat sheet made of flexible plastic material that has multiple through holes and seals the reaction containers which are arranged vertically as specified between each through hole. This flat sheet is arranged so that the through holes are positioned between the upper surface of each reaction container.
As the heating plate is lowered onto the covers of the reaction containers, the heating plate pushes down the covers and the reaction containers. Thus, they can thermally contact the metal block favorably while the PCR is conducted.
Besides, as the through holes allow the air heated between the reaction containers to circulate downward onto the metal block, condensation of vapor inside each portion of the reaction container protruding from the metal block is prevented.
Needs for gene analysis as a primary screening means are increasing because diagnosis can be made in a relatively short time. Since a large number of specimens are to be processed continuously in the primary screening, it is preferred that a series of analytical processes are automated.
If the caps and cap strips according to the afore-mentioned prior art are employed, however, it is difficult to automate the insertion of the caps into the reaction containers and to process a large number of specimens simultaneously.
The flat sheet according to Japanese Patent Application Laid-Open No. 7-5180 (1995) is an effective means for processing a certain number of specimens simultaneously in case of an independent PCR in which continuous processing is not required.
However, it is very difficult to automate the process using the flat sheet according to the Japanese Patent Application Laid-Open No. 7-5180 (1995) because the sheet must be supplied and collected in each PCR processing.
The reaction containers can be uncovered easily by a single action after the PCR is complete and the heating plate is removed, but it is a batch processing for each reaction container, where continuous processing or automation is not considered, hence difficult to achieve.
An object of the present invention is to solve the problems in the prior art and realize a reactor in which a seal material can be attached/detached to the opening of a reaction container automatically and continuously.
In order to achieve the object, the present invention is constructed as follows:
(1) In a reactor that covers the opening of a reaction container, the reactor comprises a flat plate cover that is equipped with a roller No. 1 on which sheet material is wound and a roller No. 2 which takes up the sheet material from the roller No. 1; the opening of the reaction container is covered by the sheet material positioned between the rollers No. 1 and No. 2; and, after a specified time, the opening is uncovered as the sheet material is separated from the opening of the reaction container.
(2) Preferably, in a reactor according to (1) above, the reactor further comprises a motion control unit which controls to take up a specified length of the sheet material from the roller No. 1 onto the roller No. 2 in accordance with the specified reaction in the reaction container or the temperature control of the temperature control means so that new sheet material is arranged at a position covering the opening of the reaction container.
(3) Besides, preferably, in a reactor according to (1) or (2) above, the flat plate cover further comprises a temperature control means.
(4) Besides, preferably, in a reactor according to (1) or (2) above, the reactor further comprises a sheet retainer, or a sheet retainer of a lattice shape in particular, for retaining the sheet material positioned between the rollers No. 1 and No. 2 in case multiple reaction containers are arranged.
(5) Besides, preferably, in a reactor according to (1) or (2) above, the flat plate cover further comprises a heating plate which heats the reaction container via the sheet material, and the heating plate is provided with a protrusion which is inserted into the opening of the reaction container via the sheet material and seals the opening.
Because the used sheet is collected by the revolution of the roller and, at the same time, new sheet is supplied continuously, contamination from a container to another can be prevented.
Because the seal material for the reaction container can be supplied and collected continuously, the present invention is applicable to a chemical reactor, or preferably an automatic gene analyzer including a PCR apparatus.